Alcoholic compositions having a lowered risk of acetaldehydemia

ABSTRACT

The present invention provides beverages and pharmaceutical compositions containing a deuterated alcohol according to Formula 1, and provides methods for their manufacture and use. 
                         
The compositions of the invention are expected to ameliorate some of the negative side effects associated with the consumption of alcohol, such as hangover and facial flushing.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority benefit under 35 U.S.C. § 119(e)of U.S. Provisional Patent Application Ser. No. 61/274,875 filed 21 Aug.2009; No. 61/280,860 filed 9 Nov. 2009; and, 61/283,524 filed 4 Dec.2009. The disclosure these applications are incorporated herein byreference.

FIELD OF THE INVENTION

The present invention is generally related to compositions and methodsthat diminish the negative side effects associated with the consumptionof ethanol. It is more specifically related to beverages andpharmaceutical compositions containing deuterated alcohol, and the usesthereof.

BACKGROUND OF THE INVENTION

Ethanol is the principal psychoactive constituent in alcoholicbeverages, which are usually consumed with the specific intent ofexperiencing some of ethanol's effects on the central nervous system.These effects decrease over the course of a few hours, as the ethanol isgradually metabolized by the body into acetyl CoA, a common metabolicproduct and energy source.

Metabolism of ethanol in the human body is a two-step process (Equation1), mediated by the enzymes alcohol dehydrogenase (ADH) and aldehydedehydrogenase (ALDH). Unfortunately for the consumer, the immediatemetabolite of ethanol, acetaldehyde, is toxic, mutagenic, andcarcinogenic.

It can be seen from Equation 1 that when the rate of the ALDH-catalyzedreaction (k₂) is not high enough to keep pace with the rate of theALD-catalyzed dehydrogenation of ethanol (k₂), acetaldehyde willaccumulate. High acute concentrations of acetaldehyde in vivo(acetaldehydemia) can lead to undesirable effects such as cardiovascularcomplications, drowsiness, nausea, headache, asthma and facial flushing,while chronic acetaldehydemia can lead to cirrhosis and esophagealcancer. Another unfortunate result of acute acetaldehyde toxicity, wellknown to heavy drinkers, is the hangover. A person with a hangover willexperience dizziness, fatigue, headache, nausea, muscle aches, vomiting,sensitivity to bright light, or sensitivity to noise, and most often acombination of these unpleasant symptoms, for a period of time typicallylasting from 12 to 36 hours.

It is well established that acetaldehyde is the culprit in hangovers andin alcohol-induced facial flushing, and it is the principal suspect inalcohol-associated cancers as well vide infra. Acetaldehydemia can occuras a result of heavy alcohol consumption, leading to saturation of ALDHactivity, or as a result of light or moderate alcohol consumption in thepresence of abnormally high ADH activity or inadequate ALDH activity(k₁>>k₂ in Equation 1). Inherited defects in both enzyme systems areknown to lead to acetaldehydemia-related syndromes. (D. W. Crabb, M.Matsumoto, D. Chang, M. You, Proc. Nutr. Soc. 2004, 63:49-63.)

For example, acetaldehydemia-related facial flushing after lightdrinking, or upon administration of ethanol-containing pharmaceuticalcompositions, is experienced by individuals possessing inactive orinefficient aldehyde dehydrogenase (ALDH). (S. Harada, D. P. Agarwal, H.W. Goedde, Lancet. 1981, 2:982.) Inhibition of ALDH by the drugdisulfiram creates a similar sensitivity in people having an otherwisenormally-acting enzyme. In both cases, there is a reduction of k₂ inEquation 1, resulting in a failure to clear acetaldehyde from the bloodas rapidly as it is formed, allowing its concentration to reach toxiclevels. This type of sensitivity to alcohol-induced flushing is usuallyassociated with the ALDH2*2 allele; possession of which also enhancesthe risk for esophageal cancer among drinkers. (T. Yokoyama et al.,Cancer Epidemiology, Biomarkers & Prevention 2003, 12:1227-1233).

Another means by which ethanol consumption may result in acetaldehydemiais by excessively rapid metabolism of ethanol (i.e., by increasing k₁ inEquation 1). Several studies have shown that the presence of ADH2*2alleles, which encode hyper-active forms of alcohol dehydrogenase (W. F.Bosron, T. K. Li, Hepatology, 1986 6:502-510), also contributes toalcohol flushing and a predisposition to esophageal cancer (A. Shibuyaet al., Hum. Genet. 1989, 82:14-16; T. Takeshita et al., Hum. Genet.1996, 97: 409-413; W. J. Chen et al., Alcohol. Clin. Exp. Res. 1998,22:1048-1052; A. Yokoyama et al., Alcohol. Clin. Exp. Res. 1999,23:1705-1710).

From the earliest hangover, people have struggled to find an effectiveway to treat the disagreeable physical consequences of excessive alcoholconsumption. Consumption of additional alcohol is among the oldest ofremedies; the expression “Hair of the Dog” has been attributed to the4^(th) century B. C. Greek playwright Antiphanes. (E. C. Brewer,Dictionary of Phrase and Fable, 1898). While this may temporarilyalleviate the symptoms of acetaldehydemia and alcohol withdrawal, itmerely postpones the misery and is likely to compound the damage. Othersupposedly effective interventions have included a wide variety offoods, vitamins, dietary supplements, exercises and pharmaceuticals.Compounds intended to sequester acetaldehyde in vivo have been designedand evaluated (see, e.g., H. T. Nagasawa et al., J. Med. Chem. 1987,30:1373-1378), and a wide array of unproven “supplements” andnutraceuticals are marketed to the public as hangover treatments.Notwithstanding the vast trove of folklore and anecdotal evidence, noneof these methods has ever been shown to be effective in a clinicaltrial. (M. H. Pittler et al., BMJ, 2005, 331:1515-1518.)

The alcohol-induced flush reaction (sometimes called “Asian flush”because of its relatively greater occurrence among those of Asiandescent) is a set of symptoms experienced by a person having an enzymeabnormality related to the metabolism of ethanol. When an affectedperson consumes alcohol, there is a rapid build-up of acetaldehyde inhis system, due to an aldehyde dehydrogenase deficiency and/or an excessof alcohol dehydrogenase activity. This build-up causes erythema(reddening due to capillary dilation) of the face, neck, and shoulder ofthe person; the person may also experience nausea, headaches,light-headedness, and an increased pulse rate. The sensations aresufficiently unpleasant that the affected individuals frequently refrainfrom drinking entirely, and they may be discouraged from the use ofethanol-containing pharmaceuticals. Drugmakers wishing to address thisproblem have had to surrender ethanol's advantageous physicalproperties, low cost, and relative safety. As with hangovers, thereremains a need for compositions and methods that reliably address theproblem of ethanol-induced flushing.

The deuterium isotope effect is a well-known phenomenon in the fields ofenzymology and pharmacodynamics. The primary isotope effect can beespecially large, and deuterium substitution of enzymatically-removedhydrogens can slow the rate of metabolism of substrates in vivo by afactor of two or three. In particular, it is well-established thatappropriate deuteration of a substrate, by slowing the rate ofmetabolism, can reduce the concentration of metabolites in vivo. Anearly and pertinent example is the effect of deuteration of the N-methylgroup of morphine: metabolism in vivo is slowed by a factor of abouttwo, lowering the blood level of the pharmacologically active metaboliteand causing a corresponding reduction in analgesic potency (C. Elison etal., Science, 1961, 1078-1079).

Deuterated drugs have been the subject of a number of patentapplications. U.S. Pat. No. 5,223,269 to Liepins describes methods andcompositions for treating hypertension. U.S. Pat. No. 5,838,375 toFurminger describes pharmaceutical compositions containing a biologicalagent and D₂O to improve the stability of the agent. U.S. Pat. No.5,895,660 to Hoffmann describes deuterated drugs for transdermalapplications. U.S. Pat. No. 6,376,531 describes deuteratedpharmaceuticals for the treatment of psychiatric disorders. The contentsof these patents are incorporated by reference into this document intheir entirety, for all purposes.

The hydrogen atoms at C-1 in ethanol are enantiotopic; by convention theoxygen and the C-1 and C-2 carbons define a plane which divides thesurrounding space, and the hydrogen residing in the “Si” half-space isspecified as H(Si) or H_(Si). The hydrogen in the “Re” half-space isdesignated as H(Re) or H_(Re). In the case of ethanol, an alternativeterminology designates H_(Re) as the “pro-R” hydrogen, and H_(Si) as“pro-S”. The absolute stereochemistry is shown below:

In the course of oxidation by a mammalian alcohol dehydrogenase, H_(Re)of ethanol is stereospecifically removed and transferred to the enzymecofactor NAD, with concurrent abstraction of the hydroxyl proton. Thisproduces acetaldehyde as the product, in which H_(Si) has been retainedas the aldehydic hydrogen.

Remarkably, despite thousands of years of effort directed to lesseningthe unpleasant effects of excess ethanol consumption, and more recentattempts to alleviate problems associated with administration ofethanol-containing pharmaceutical formulations, there is still a needfor compositions and methods that effectively address these problems.

SUMMARY OF THE INVENTION

The present invention provides an alcoholic composition, such as abeverage or a pharmaceutical formulation, wherein at least 5 molepercent of the ethanol in the composition is deuterated ethanol whereinH_(Re) is deuterium, as shown in Formula 1.

It should be understood that in Formula 1, and in all other structuresrepresented herein, each atom designated “H” without a superscript mayindependently be hydrogen (¹H) or deuterium (²H). The terms “²H” and “D”are used interchangeably to refer specifically to deuterium.

The present invention also provides methods for increasing the timeperiod between the consumption of an alcoholic beverage and theattainment of peak blood levels of ethanol, and methods for delaying theonset of ethanol-induced symptoms associated with the consumption ofalcoholic beverages, which comprise the consumption of an alcoholicbeverage containing a deuterated ethanol. The invention also providesmethods for ameliorating acetaldehydemia and its symptoms, whichcomprise the consumption of the alcohol-containing beverages andpharmaceutical compositions of the invention.

BRIEF DESCRIPTION OF THE FIGURE

FIG. 1 shows the time course of blood alcohol levels in a human subjectafter administration of ordinary beverage ethanol (♦) and1,1-dideuterioethanol (▪).

DETAILED DESCRIPTION OF THE INVENTION

The present invention takes advantage of the surprising discovery thatthe rate of absorption of orally-administered ethanol in a human subjectis significantly reduced if the ethanol is deuterated (FIG. 1). Peakblood concentrations of ethanol, which normally are reached 20-30minutes after ingestion, are delayed to 1-2 hours after ingestion, andpeak concentrations are reduced by 15-20%. (The biochemical basis forthis unexpected sensitivity to molecular weight is not presently known.)Peak acetaldehyde blood levels are delayed and reduced as well, becausethe rate of oxidation by alcohol dehydrogenase is a function of theconcentration of ethanol.

The invention provides an alcoholic composition, such as a beverage or apharmaceutical formulation, wherein at least 5 mole percent of theethanol in the composition is deuterated ethanol wherein H_(Re) isdeuterium, as shown in Formula 1:

As noted above, each atom designated “H” may independently be hydrogen(¹H) or deuterium (²H). Specific examples of suitable deuteratedethanols include, but are not limited to, ethanol-1-D (Formula 2),ethanol-1,1-D₂ (Formula 3), ethanol-1,2-D₂, (Formula 4), and ethanol-D₅(CD₃CD₂OH). The enantiomer of the ethanol-1-D illustrated in formula 2may be present in the compositions of the invention.

In successively more-preferred embodiments, the compositions compriseethanol wherein at least 15 mole percent, 30 mole percent, 50 molepercent, 75 mole percent, or 95 mole percent of the ethanol is adeuterated alcohol according to Formula 1.

In additional embodiments, the present invention also takes advantage ofthe fact that the removal of H_(Re) from ethanol by alcoholdehydrogenase is subject to a substantial primary deuterium isotopeeffect. Specifically, a deuterium (²H) in the H_(Re) position is removedby alcohol dehydrogenase two to four times more slowly than a light (¹H)hydrogen. This effect has been thoroughly documented both in vitro (B.V. Plapp et al., J. Biol. Chem. 1973, 248:3470; Lundquist et al.,Alcohol Clin. Exp. Res. 1986, 10 (6th Suppl): 69S-72S; J. O. Winberg etal., Biochem. Mol. Biol. Int. 1993, 31:651-658) and in vivo (S. E.Damgaard, Biochemistry 1981, 20:5662-5669; J. Alderman et al., J. Biol.Chem. 1987, 262:7497-7503; F. Lundquist et al., Pharmacol. Toxicol. 198965:55-62).

Due to the primary deuterium isotope effect, an individual having agreater-than-normal level of alcohol dehydrogenase activity, andconsequently having a propensity to alcohol-induced flushing, uponconsumption of an alcoholic composition of the invention, shouldmetabolize the deuterated ethanol of Formula 1 at a significantly slowerrate than he or she would metabolize ethanol having a natural isotopicabundance at H_(Re). Because the kinetic isotope effect produces alowering of k₁ in Equation 1, the individual's rate of production ofacetaldehyde in vivo should be shifted back toward the rate observed innormal individuals. The result should be a reduced level of acetaldehydein the individual's system, with a corresponding reduction in theseverity of symptoms of acetaldehydemia, such as hangover andalcohol-induced flushing. The greater the proportion of deuterium atH_(Re) in the ethanol, the greater the expected reduction inacetaldehyde concentration in the blood.

The reduction in acetaldehyde blood levels should be especiallypronounced if the individual can metabolize the ADH-generatedacetaldehyde at a rate that prevents accumulation of the aldehyde. Themetabolism of acetaldehyde to acetate is carried out by aldehydedehydrogenase (ALDH), and to a certain extent by cytochrome P450. SomeALDH enzymes exhibit a deuterium isotope effect when operating oncertain substrates, such as benzaldehydes (M. Scharschmidt et al.,Biochemistry 1984, 23:5471-5478) and glyceraldehyde-3-phosphate (P. F.Canellas and W. W. Cleland, Biochemistry 1991, 30:8871-8876). On theother hand, sheep liver ALDH shows no isotope effect when acting uponacetaldehyde-1-d (CH₃CDO) (G. J. Hart and F. M. Dickinson, Biochem. J.1978, 175:899-908), and horse liver ALDH shows no isotope effect whenacting upon propionaldehyde-1-d (CH₃CH₂CDO) (R. I. Feldman and H.Weiner, J. Biol. Chem. 1972, 247:267-272). In order to avoid anypossible reduction in ALDH activity, it can be desirable to have littleor no deuterium at H_(Si) in the compound of Formula 1, andcorrespondingly little or no production of CH₃CDO. It should however beunderstood that lowering the in vivo acetaldehyde concentration byproviding deuterium at H_(Re) of ethanol, by the methods of the presentinvention, should reduce the symptoms of acetaldehydemia regardless ofthe isotopic composition of H_(Si).

It will be appreciated that even in individuals not suffering from anenzyme abnormality, consumption of the compositions of the invention inplace of equivalent prior art beverages and pharmaceutical formulationsshould still lead to slower formation of acetaldehyde in vivo, withattendant reduction of the symtoms of acetaldehydemia. The slowermetabolism of the deuterated alcohol of the invention, in combinationwith the extended period of peak blood alcohol concentration, shouldreduce the amount of alcohol needed to produce a givenpsychopharmacological effect. The beverages of the present invention,accordingly, can be manufactured with a lower alcohol content thanequivalent prior art beverages without being perceived by consumers as“weaker” or less potent, and they should produce a more consistent andprolonged effect with a less-pronounced initial effect. In particular,the beverages of the invention may be consumed on an empty stomach, withless risk of a sudden onset of inebriation.

Conversely, pharmaceutical compositions can be produced having higherethanol concentrations and greater solvent power than prior artcompositions, without an increase in acetaldehyde-induced side-effects.The greater solvent power enables the production of more concentratedformulations, with attendant savings and convenience.

The present invention thus provides methods for avoiding, or reducingthe severity of, ethanol-induced acetaldehydemia, hangover and facialflushing, by providing and/or consuming the alcoholic beverages andpharmaceutical compositions of the invention.

The present invention also provides a method of making an alcoholicbeverage. The method comprises the step of adding to a beverage adeuterated alcohol according to Formula 1, in an amount sufficient toproduce an alcoholic beverage comprising water and ethanol wherein atleast 5 mole percent of the ethanol is a deuterated alcohol according toFormula 1. In additional embodiments, a deuterated alcohol according toFormula 1 is added in an amount sufficient to produce an alcoholicbeverage comprising water and ethanol wherein at least 15 mole percent,30 mole percent, 50 mole percent, 75 mole percent, or 95 mole percent ofthe ethanol is a deuterated alcohol according to Formula 1.

The present invention also provides a method of making an alcoholicpharmaceutical composition. The method comprises the step of combiningan active pharmaceutical ingredient (API) with a deuterated alcoholaccording to Formula 1, in an amount sufficient to produce a compositionwherein at least 5 mole percent of the ethanol in the composition is adeuterated alcohol according to Formula 1. In additional embodiments,the deuterated alcohol according to Formula 1 is combined in an amountsufficient to produce a composition wherein at least 15 mole percent, 30mole percent, 50 mole percent, 75 mole percent, or 95 mole percent ofthe ethanol in the composition is a deuterated alcohol according toFormula 1. Pharmaceutically acceptable excipients may be introduced oradmixed with the deuterated ethanol and/or the API, prior to orfollowing the combining step.

In the present document, the use of “H” refers to the genus of hydrogenatoms, of any isotopic composition, i.e. ¹H, ²H, or any combinationthereof in any proportions. The use of “D” or “²H” refers specificallyto the deuterium isotope. Proportions described herein by percentagesare percent by weight unless otherwise indicated.

“Alcohol” refers to ethanol.

“Alcopop” refers to certain flavored alcoholic beverages, including:malt beverages to which various fruit juices or other flavorings havebeen added; beverages containing wine to which ingredients such as fruitjuice or other flavorings have been added (e.g., wine coolers); andbeverages containing distilled alcohol and added ingredients such asfruit juices or other flavorings.

“Almost sake” refers to sake infused with fruit flavors. One example of“almost sake” is Hana flavored sake produced by Takara Sake.

“Awamori” refers to a distilled spirit derived from long grain rice thatis typically made in Okinawa.

“Baijiu” refers to a distilled spirit made from sorghum, wheat orglutinous rice. It typically has an alcohol content of about 60%.

“Beer” refers to an alcoholic beverage produced by the brewing andfermentation of starches, which are primarily derived from cereal grains(e.g., malted barley, wheat, corn and rice). The alcohol content of beertypically ranges from one percent to six percent.

“Alcoholic beverage” refers to a liquid suitable for human consumption,which contains ethanol, water, and at least one additional component,which is a sweetener, odorant, or flavorant, or a congener derived fromthe brewed or fermented compositions from which the beverage isproduced. The amount of ethanol is at least 1% by weight. In variousother embodiments of the invention, the amount of ethanol is at least2%, 5%, 10%, 20%, or 40% by weight. “Deuterated alcohol,” in the contextof this document, refers to ethanol having at least one deuterium atom,and corresponding to Formula 1. Deuterated alcohols are articles ofcommerce sold by vendors such as CDN Isotopes, Inc., Pointe-Claire,Quebec, Canada, and methods for making such compounds are well known tothose of skill in the art. Ethanol stereospecifically deuterated at theH_(Re) position is known (see Damgaard et al., Biochemistry, 198120:5662-9, and references therein), while racemic ethanol-1-d is readilyobtained by reduction of acetaldehyde with BD₃ or NaBD₄. Non-specifichydrogen-deuterium exchange reactions are referenced and/or discussed inU.S. Pat. No. 7,517,990, which is incorporated by reference into thisdocument in its entirety for all purposes, and particularly for thepurpose of disclosing methods of deuterium incorporation. Hydrogenationof a vinyl ester (e.g., vinyl acetate) with D₂ gas, followed byhydrolysis, will provide ethanol-1,2-d₂ having at least 50% D at theH_(Re) position, the proportion of D at this position may be raised, ifdesired, by the use of an asymmetric hydrogenation catalyst. (See, e.g.,G. J. Clarkson et al., Tetrahedron: Asymmetry, 2004, 15:1787-1792.)

“Enzyme abnormality” in the context of metabolism of ethanol refers toeither a decreased aldehyde dehydrogenase level or an increased level ofactivity of alcohol dehydrogenase, or both, which results in higher thannormal levels of acetaldehyde in the body of an affected person.Although this is most commonly the result of allelic variations in thegenes encoding the enzymes, other causes (e.g. misregulation of geneexpression) are encompassed by the present invention.

References herein to methods of “avoiding” or “reducing the severity” ofsymptoms of acetaldehydemia should be understood to refer to anavoidance or reduction relative to the symptoms that would beexperienced with an equivalent dose of a non-deuterated composition.

“Fermentation byproduct” refers to non-ethanol compounds produced as theresult of starch fermentation.

“Han” refers to a liquor made from barley vodka that has been distilledmultiple times and mixed with polished rice. It is not diluted withwater.

“Pharmaceutical composition” refers to a liquid composition, suitablefor administration to humans, comprising an active pharmaceuticalingredient, ethanol, and optionally water and/or other pharmaceuticallyacceptable excipients.

“Sake” refers to an alcohol-based drink produced by multiple, parallelfermentation of polished rice. There are two basic types of sake:futsu-shu, which is oftentimes referred to as “ordinary sake”; and,tokutei meisho-shu, which is a premium sake oftentimes referred to as“special designation sake”. Honjozo-shu, Junmai-shu and Ginjo-shu arecategories of premium sake. Honjozo-shu includes a processing step ofadding a slight amount of brewer's alcohol to sake before pressing.Junmai-shu, or “pure rice sake”, is made simply from rice, water andkoji mold (Aspergillus oryzae); no brewer's yeast or other additives areincluded in the production process. Ginjo-shu is made from rice that hasbeen polished to 60% or less of its original weight.

“Shochu” refers to a distilled spirit made from barley, sweet potatoes,cane sugar, or rice. It typically has an alcohol content of 25% or more.

“Soju” refers to a distilled spirit traditionally made from rice with analcohol content ranging from 25% to 45%. In some varieties, themanufacturing process involves the fermentation of potatoes, barley,wheat, sweet potatoes or tapioca instead of rice.

“Spirits” refers to alcoholic beverages produced by the fermentation ofstarches and subsequent distillation. The starches are usually derivedfrom a variety of natural sources (e.g., agave, potato, beets, un-maltedcereal grain), and spirits typically have an alcohol content greaterthan twenty percent. The term encompasses distilled spirits such asvodka, gin, whisky, rye, cognac, brandy, bourbon, rum, tequila, and thelike.

“Wine” refers to an alcoholic beverage produced by the fermentation ofsugars and starches, primarily derived from fruits (e.g., grapes). Thealcohol content of wine typically ranges from nine percent to sixteenpercent. Fortified wines, having higher alcohol content, are encompassedwithin the term as well.

Compositions

Compositions of the present invention are beverages and pharmaceuticalformulations that comprise a deuterated alcohol according to Formula 1.Typically, the compositions comprise between 0.25 percent and 60.0percent by weight of the deuterated alcohol.

Where the beverage is an alcopop, it typically comprises between 0.25percent and 20.0 percent of the deuterated alcohol. Oftentimes, thebeverage comprises between 0.5 percent and 15.0 percent of thedeuterated alcohol. In specific cases, the beverage may comprise any ofthe following ranges of deuterated alcohol: 1.0 percent to 15.0 percent;2.0 percent to 15.0 percent; 3.0 percent to 15.0 percent; 4.0 percent to15.0 percent; 4.0 percent to 14.0 percent; 4.0 percent to 13.0 percent;4.0 percent to 12.0 percent; 4.0 percent to 11.0 percent; 4.0 percent to10.0 percent; 4.0 percent to 9.0 percent; and 4.0 percent to 8.0percent.

Where the beverage is beer, it typically comprises between 0.25 percentand 15.0 percent of the deuterated alcohol. Oftentimes, the beveragecomprises between 0.5 percent and 12.0 percent of the deuteratedalcohol. In specific cases, the beverage may comprise any of thefollowing ranges of deuterated alcohol: 1.0 percent and 12.0 percent;2.0 percent and 12.0 percent; 3.0 percent and 12.0 percent; 3.0 percentand 11.0 percent; 3.0 percent and 10.0 percent; 3.0 percent and 9.0percent; 3.0 percent and 8.0 percent; 3.0 percent and 7.0 percent; and,3.0 percent and 6.0 percent.

Where the beverage is wine, it typically comprises between 0.25 percentand 15.0 percent of the deuterated alcohol. Oftentimes, the beveragecomprises between 0.5 percent and 12.0 percent of the deuteratedalcohol. In specific cases, the beverage may comprise any of thefollowing ranges of deuterated alcohol: 1.0 percent and 12.0 percent;2.0 percent and 12.0 percent; 3.0 percent and 12.0 percent; 4.0 percentand 12.0 percent; 5.0 percent and 12.0 percent; 6.0 percent and 12.0percent; 3.0 percent and 11.0 percent; 3.0 percent and 10.0 percent; 3.0percent and 9.0 percent; 3.0 percent and 8.0 percent; 3.0 percent and7.0 percent; and, 3.0 percent and 6.0 percent.

Where the beverage is a spirit, it typically comprises between 20.0percent and 60.0 percent of the deuterated alcohol. Oftentimes, thebeverage comprises between 25.0 percent and 50.0 percent of thedeuterated alcohol. In specific cases, the beverage may comprise any ofthe following ranges of deuterated alcohol: 20.0 percent to 50.0percent; 20.0 percent to 45.0 percent; 20.0 percent to 40.0 percent;20.0 percent to 35.0 percent; and 20.0 percent to 30.0 percent.

Where the beverage is sake, it typically comprises between 0.25 percentand 20.0 percent of the deuterated alcohol. Oftentimes, the beveragecomprises between 0.25 percent and 17.5 percent of the deuteratedalcohols. In certain cases, the beverage may comprise any of thefollowing ranges of deuterated alcohol: 1.0 percent to 15.0 percent; 1.0percent to 12.5 percent; 1.5 percent to 10.0 percent; 2.0 percent to10.0 percent; and 2.5 percent to 10.0 percent.

Where the beverage is awamori, it typically comprises between 0.25percent and 35.0 percent of the deuterated alcohol. Oftentimes, thebeverage comprises between 0.25 percent and 30.0 percent of thedeuterated alcohol. In certain cases, the beverage may comprise any ofthe following ranges of deuterated alcohol: 1.0 percent to 27.5 percent;1.5 percent to 25.0 percent; 2.0 percent to 20.0 percent; 2.5 percent to17.5 percent; and 2.5 percent to 15.0 percent.

Where the beverage is baijiu, it typically comprises between 0.25percent and 65.0 percent of the deuterated alcohol. Oftentimes, thebeverage comprises between 0.25 percent and 60.0 percent of thedeuterated alcohol. In specific cases, the beverage may comprise any ofthe following ranges of deuterated alcohols: 1.0 percent to 55.0percent; 1.5 percent to 50.0 percent; 2.0 percent to 45.0 percent; 2.5percent to 40.0 percent; 3.0 percent to 35.0 percent; and 3.5 percent to30.0 percent.

Where the beverage is han, it typically comprises between 0.25 percentand 55.0 percent of the deuterated alcohol. Oftentimes, the beveragecomprises between 0.25 percent and 50.0 percent of the deuteratedalcohol. In specific cases, the beverage may comprise any of thefollowing ranges of deuterated alcohol: 1.0 percent to 45.0 percent; 1.5percent to 40.0 percent; 2.0 percent to 35.0 percent; 2.5 percent to30.0 percent; and 3.0 percent to 25.0 percent.

Where the beverage is shochu, it typically comprises between 0.25percent and 35.0 percent of the deuterated alcohol. Oftentimes, thebeverage comprises between 0.25 percent and 30.0 percent of thedeuterated alcohol. In specific cases, the beverage may comprise any ofthe following ranges of deuterated alcohol: 1.0 percent to 25.0 percent;1.5 percent to 22.5 percent; 2.0 to 20.0 percent; 2.5 percent to 17.5percent; 3.0 percent to 15.0 percent; and 3.5 percent to 12.5 percent.

Where the beverage is soju, it typically comprises between 0.25 percentand 50.0 percent of the deuterated alcohol. Oftentimes, the beveragecomprises between 0.25 percent and 45.0 percent of the deuteratedcompound. In specific cases, the beverage may comprise any of thefollowing ranges of deuterated alcohol: 1.0 percent to 40.0 percent; 1.5percent to 35.0 percent; 2.0 percent to 30.0 percent; 2.5 percent to25.0 percent; and 2.5 percent to 20.0 percent.

Where the beverage is almost sake, it typically comprises between 0.25percent and 12.0 percent of the deuterated alcohol. Oftentimes, thebeverage comprises between 0.25 percent and 11.0 percent of thedeuterated alcohol. In specific cases, the beverage may comprise any ofthe following ranges of deuterated alcohol: 1.0 percent to 10.0 percent;1.5 percent to 9.0 percent; 2.0 percent to 8.0 percent; 2.5 percent to7.5 percent; 3.0 percent to 7.0 percent; and 3.5 percent to 6.0 percent.

The various beverages include mixtures of non-deuterated ethanol and adeuterated ethanol of Formula 1, usually in ratios ranging from 1/10 to10/1. The non-deuterated ethanol can be obtained, for instance, fromcompositions derived from fermentation, brewing and fermentation, and/orfermentation and subsequent distillation.

For instance, where the beverage is an alcopop containing bothdeuterated and non-deuterated ethanol, non-limiting examples ofdeuterated to non-deuterated alcohol mixture ratios, by weight, include:1/10; 1/9; 1/8; 1/7; 1/6; 1/5; 1/4; 1/3; 1/2; 1/1; 2/1; 3/1; 4/1; 5/1;6/1; 7/1; 8/1; 9/1; and, 10/1.

Where the beverage is beer containing both deuterated and non-deuteratedethanol, non-limiting examples of deuterated to non-deuterated alcoholmixture weight ratios include: 1/10; 1/9; 1/8; 1/7; 1/6; 1/5; 1/4; 1/3;1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1; 9/1; and, 10/1.

Where the beverage is wine containing both deuterated and non-deuteratedethanol, non-limiting examples of deuterated to non-deuterated alcoholmixture weight ratios include: 1/10; 1/9; 1/8; 1/7; 1/6; 1/5; 1/4; 1/3;1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1; 9/1; and, 10/1.

Where the beverage is a spirit containing both deuterated andnon-deuterated ethanol, non-limiting examples of deuterated tonon-deuterated alcohol mixture weight ratios include: 1/10; 1/9; 1/8;1/7; 1/6; 1/5; 1/4; 1/3; 1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1;9/1; and, 10/1.

Where the beverage is sake containing both deuterated and non-deuteratedethanol, non-limiting examples of deuterated to non-deuterated alcoholmixture weight ratios include: 1/10; 1/9; 1/8; 1/7; 1/6; 1/5; 1/4; 1/3;1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1; 9/1; and, 10/1.

Where the beverage is awamori containing both deuterated andnon-deuterated ethanol, non-limiting examples of deuterated tonon-deuterated alcohol mixture weight ratios include: 1/10; 1/9; 1/8;1/7; 1/6; 1/5; 1/4; 1/3; 1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1;9/1; and, 10/1.

Where the beverage is baijiu containing both deuterated andnon-deuterated ethanol, non-limiting examples of deuterated tonon-deuterated alcohol mixture weight ratios include: 1/10; 1/9; 1/8;1/7; 1/6; 1/5; 1/4; 1/3; 1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1;9/1; and, 10/1.

Where the beverage is han containing both deuterated and non-deuteratedethanol, non-limiting examples of deuterated to non-deuterated alcoholmixture weight ratios include: 1/10; 1/9; 1/8; 1/7; 1/6; 1/5; 1/4; 1/3;1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1; 9/1; and, 10/1.

Where the beverage is shochu containing both deuterated andnon-deuterated ethanol, non-limiting examples of deuterated tonon-deuterated alcohol mixture weight ratios include: 1/10; 1/9; 1/8;1/7; 1/6; 1/5; 1/4; 1/3; 1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1;9/1; and, 10/1.

Where the beverage is soju containing both deuterated and non-deuteratedethanol, non-limiting examples of deuterated to non-deuterated alcoholmixture weight ratios include: 1/10; 1/9; 1/8; 1/7; 1/6; 1/5; 1/4; 1/3;1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1; 9/1; and, 10/1.

Where the beverage is almost sake containing both deuterated andnon-deuterated ethanol, non-limiting examples of deuterated tonon-deuterated alcohol mixture weight ratios include: 1/10; 1/9; 1/8;1/7; 1/6; 1/5; 1/4; 1/3; 1/2; 1/1; 2/1; 3/1; 4/1; 5/1; 6/1; 7/1; 8/1;9/1; and, 10/1.

EXAMPLES

By way of illustration, representative examples of various beveragesaccording to the present invention are provided below.

Example 1

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 100 percent.

Percentage of non-deuterated ethanol: 0 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 2

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 90 percent.

Percentage of non-deuterated ethanol: 10 percent.

Other Ingredients: water; sugar; fruit juice and/or soda.

Example 3

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 80 percent.

Percentage of non-deuterated ethanol: 20 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 4

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 70 percent.

Percentage of non-deuterated ethanol: 30 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 5

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 60 percent.

Percentage of non-deuterated ethanol: 40 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 6

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 50 percent.

Percentage of non-deuterated ethanol: 50 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 7

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 40 percent.

Percentage of non-deuterated ethanol: 60 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 8

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 30 percent.

Percentage of non-deuterated ethanol: 70 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 9

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 20 percent.

Percentage of non-deuterated ethanol: 80 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 10

Beverage type: alcopop.

Total ethanol content (deuterated and non-deuterated): 4.0 percent to8.0 percent.

Percentage of deuterated ethanol: 10 percent.

Percentage of non-deuterated ethanol: 90 percent.

Other ingredients: water; sugar; fruit juice and/or soda.

Example 11

Pharmaceutical composition: Aromatic Elixir, U.S.P.

Total ethanol content (deuterated and non-deuterated): 22 percent.

Percentage of deuterated ethanol: 90 percent.

Percentage of non-deuterated ethanol: 10 percent.

Other ingredients: water, sugar, orange oil, lemon oil, coriander oil,and anise oil.

By way of example, the following pharmaceutical compositions may beprepared substantially as is currently known in the art, but withsubstitution of a deuterated ethanol of Formula 1 for 50% to 100% of thetotal ethanol in the composition:

Ethanol content Brand name API (%) Anbesol ™ benzocaine (20%) 70 AsbronG ™ Elixir guaifenesin (6.7 mg/ml) 15 theophylline glycinate (20 mg/ml)Diphenhydramine Elixir diphenhydramine HCl (2.5 mg/ml) 14 Bronkolixir ™ephedrine sulfate (2.4 mg/ml) 19 guaifenesin (10 mg/ml) phenobarbital(0.8 mg/ml) theophylline (3 mg/ml) chlorpheniramine maleate (0.2 mg/ml)Choedyl ™ Elixir oxtriphylline (20 mg/ml) 20 CONTAC ™ Nighttimeacetaminophen (33 mg/ml) 25 chlorpheniramine maleate (.13 mg/ml))dextromethorphan HBr (1 mg/ml) pseudoephedrine HCl (2 mg/ml) Donnatal ™Elixir phenobarbital (3 mg/ml) 23 hyoscyamine sulfate (21 ug/ml)atropine sulfate (3.9 ug/ml) scopolamine HBr (1.3 ug/ml) Elixophyllin ™Elixir theophylline (5.3 mg/ml) 20 Lasix ™ Oral Solution furosemide (10mg/ml) 11.5 Lomotil ™ Liquid diphenoxylate HCl (5 mg/ml) 15 atropinesulfate (5 ug/ml) Lufyllin ™ Elixir dyphylline (10.7 mg/ml) 20Nicotinex ™ niacin (10 mg/ml) 14 Nucofed ™; Tussar ™ SF codeinephosphate (2 mg/ml) 12.5 pseudoephedrine HCl (6 mg/ml) guaifenesin (20mg/ml) Organidin ™ Elixir guaifenesin (40 mg/ml) 22 dextromethorphan HBr(4 mg/ml) Phenobarbital Elixir phenobarbital (3 mg/ml) 13.5 Prolixin ™Elixir fluphenazine HCl (0.5 mg/ml) 14 Robitussin ™ Night Reliefacetaminophen (22 mg/ml) 25 dextromethorphan HBr (1 mg/ml)pseudoephedrine HCl (2 mg/ml) pyrilamine maleate (1.7 mg/ml)Sandimmune ™ Oral cyclosporine (100 mg/ml) 12.5 Sominex ™ Liquiddiphenhydramine HCl 10 (12.5 mg/ml) Tussend ™ Expectorantchlorpheniramine maleate 12.5 (0.4 mg/ml) hydrocodone bitartrate (0.5mg/ml) pseudoephedrine HCl (6 mg/ml) Vicks Nyquil ™ doxylamine succinate(0.4 mg/ml) 25 acetaminophen (33 mg/ml) pseudoephedrine HCl (2 mg/ml)dextromethorphan HBr (1 mg/ml)Methods

The present invention provides a method of making an alcoholic beverage.The method comprises the step of adding to an alcoholic, non-alcoholic,or reduced-alcohol beverage a deuterated alcohol according to Formula 1,in an amount sufficient to produce a beverage comprising water andethanol wherein at least 5 mole percent of the ethanol is a deuteratedalcohol according to Formula 1. In another embodiment, a deuteratedalcohol according to Formula 1 is added in an amount sufficient toproduce a beverage comprising water and ethanol wherein at least 15 molepercent of the ethanol is a deuterated alcohol according to Formula 1.In another embodiment, a deuterated alcohol according to Formula 1 isadded in an amount sufficient to produce a beverage comprising water andethanol wherein at least 30 mole percent of the ethanol is a deuteratedalcohol according to Formula 1. In another embodiment, a deuteratedalcohol according to Formula 1 is added in an amount sufficient toproduce a beverage comprising water and ethanol wherein between 50 and100 mole percent of the ethanol is a deuterated alcohol according toFormula 1.

The present invention also provides a method of making an alcoholicpharmaceutical composition. The method comprises the step of adding toan active pharmaceutical ingredient a deuterated alcohol according toFormula 1, in an amount sufficient to produce, after all otheringredients have been incorporated, a pharmaceutical composition whereinat least 5 mole percent of the ethanol in the composition is adeuterated alcohol according to Formula 1. In another embodiment, adeuterated alcohol according to Formula 1 is added in an amountsufficient to produce a pharmaceutical composition wherein at least 15mole percent of the ethanol in the composition is a deuterated alcoholaccording to Formula 1. In another embodiment, a deuterated alcoholaccording to Formula 1 is added in an amount sufficient to produce apharmaceutical composition wherein at least 30 mole percent of theethanol in the composition is a deuterated alcohol according toFormula 1. In another embodiment, a deuterated alcohol according toFormula 1 is added in an amount sufficient to produce a pharmaceuticalcomposition wherein between 50 and 100 mole percent of the ethanol inthe composition is a deuterated alcohol according to Formula 1.

Practitioners of the present invention will appreciate that the benefitsof increasing the mole fraction of deuterated ethanol will be obtainedat correspondingly higher cost, and that profitable use of the inventionin commercially marketed products will entail a trade-off betweenbenefits and costs.

Beverages according to the present invention are typically made byadding one or more of the deuterated alcohols to other ingredients. Inthe case of Example 6 above, for example, one could mix suitable amountsof fruit juice, water, sugar and non-deuterated ethanol (e.g., maltliquor or vodka) together, followed by the addition of the correctamount of deuterated alcohol needed to arrive at a beverage containing 4percent to 8 percent ethanol, with 50 percent of the ethanol beingdeuterated alcohol.

Beer and wine beverages are typically made by adding a suitable amountof the deuterated alcohol of Formula 1 to either beer or wine that has areduced alcohol content. For instance, if a beer is desired that has a 6percent ethanol content, one would obtain a reduced-alcohol beer (e.g.,beer containing 3.2% non-deuterated ethanol) or a non-alcoholic beer,and add an amount of deuterated ethanol such that the overall ethanolcontent (i.e., deuterated plus non-deuterated) is 6 percent.

Spirits are available with a variety of alcohol contents. As with beerand wine, one can make a spirit beverage according to the presentinvention by adding deuterated ethanol to a spirit having less than thedesired amount of ethanol—e.g., adding deuterated ethanol such that theoverall alcohol content of a spirit is increased from 20 percent(non-deuterated) ethanol to 40 percent.

Sake, awamori, baijiu, han, shochu, soju, and “almost sake” beveragesaccording to the present invention are preferably made by adding asuitable amount of a deuterated alcohol of Formula 1 to areduced-alcohol version of the beverage. For instance, if a sake isdesired that has a 15 percent ethanol content, one may obtain areduced-alcohol sake and add an amount of deuterated ethanol accordingto Formula 1 such that the overall ethanol content (deuterated plusnon-deuterated) is 15 percent. Examples of suitable reduced-alchoholsakes include, but are not limited to, sparkling sakes such as POOCHIPOOCHI™ (Junmai Sparking Sake, Suehiro Sake Brewery (Tohoku, Fukushima),alcohol content 7.5%), TANZAN JAPON™ (Junmai Sparkling Sake, TanzanShuzo (Kinki, Kyoto), alcohol content 8.0%), HANA AWAKA™ (JunmaiSparkling Sake, Ozeki Corporation (Kinki, Hyogo), alcohol content 7.0%),and SAWASAWA™ (Junmai Sparkling Sake, Choryo (Kinki, Nara), alcoholcontent 8.0-9.0%).

Methods of making reduced-alcohol beer and wine are also well known tothose of ordinary skill in the art. Non-alcoholic and “light” beers, inparticular, are well-known articles of commerce. A description relatedto the production of low-alcohol beer is presented in United StatesPatent Publication No. 20070116801 and references therein; a descriptionregarding the production of low-alcohol wine appears in U.S. Pat. No.4,681,767 and references therein. Both of these patent documents areincorporated by reference into this document in their entireties, forall purposes.

Methods of making reduced-alcohol sake are also well known to those ofordinary skill in the art. A description related to the production oflow-alcohol sake is presented in “Development of Low Alcohol Sake” OnkoChishin, 2004, pp 58-62.

A method of producing low-alcohol beverages which has generalapplicability is discussed in U.S. Pat. No. 4,612,196 (“Preparation ofLow Alcohol Beverages by Reverse Osmosis”), which is incorporated byreference into this document in its entirety, for all purposes.

The present invention provides a method of reducing the severity of ahangover in a person to whom the practitioner is serving alcoholicbeverages. The method comprises providing to that person an alcoholicbeverage comprising water and ethanol, wherein at least 5 mole percentof the ethanol is a deuterated alcohol according to Formula 1.

In another embodiment, the present invention provides a method ofreducing the symptoms of alcohol-induced facial flushing in a person towhom the practitioner is serving alcoholic beverages. The methodcomprises providing to that person an alcoholic beverage comprisingwater and ethanol, wherein at least 5 mole percent of the ethanol is adeuterated alcohol according to Formula 1. Drinking beverages of thepresent invention is expected to provide for a reduction in disagreeableacetaldehydemia-related physical effects in the drinker, compared to theeffects of drinking an equivalent amount of similar beverages where allthe ethanol in the beverage is non-deuterated. This is especially truefollowing the consumption of such beverages to an extent that ordinarilyresults in a hangover. Consumption of the instant beverages shouldtypically reduce one or more hangover symptoms by at least 3 percent, asmeasured by a standardized scale in a human or animal model.Non-limiting symptoms associated with a hangover include dizziness,fatigue, headache, nausea, muscle aches, vomiting, sensitivity to brightlight, and sensitivity to noise. Animal models related to such symptomsare described in R. D. Prediger et al. “Activation of adenosine A1receptors reduces anxiety-like behavior during acute ethanol withdrawal(hangover) in mice.” Neuropsychopharmacology, 2006, 31(10):2210-2220; H.C. Becker, “Animal Models of Alcohol Withdrawal.” Alcohol Research &Health, 2000, 24(2):105-110.

Depending on the relative deuterium content and total amount of ethanolconsumed, consumption of beverages according to the present inventionwill reduce one or more hangover symptoms by at least 5.0 percent, 7.5percent or 10.0 percent. In favorable cases, such consumption reducesthe symptoms by at least 15.0 percent, 20.0 percent or 25.0 percent.

Consumption of beverages according to the present invention furthermoreshould reduce one or more alcohol flush symptoms by at least 5 percent,as measured by a standardized scale in a human or animal model.Non-limiting symptoms associated with alcohol flush include skinredness, nausea, headaches, light-headedness, and increased pulse rate.Suitable measures of flushing are described, for example, in A. K.Kawata et al., “Flushing ASsessment Tool (FAST): psychometric propertiesof a new measure assessing flushing symptoms and clinical impact ofniacin therapy,” Clinical Drug Investigation, 2009, 29(4):215-229.

Depending on the relative deuterium content and total amount of ethanolconsumed, and upon the genotype and phenotype of the individual,consumption of the beverages and pharmaceutical compositions of theinvention may reduce one or more alcohol flush symptoms by at least 5.0percent, 7.5 percent or 10.0 percent. In favorable cases, suchconsumption reduces the symptoms by at least 15.0 percent, 20.0 percentor 25.0 percent.

Compositions of the present invention provide for new methods ofmarketing beverages containing alcohol. In one method, one communicatesto a consumer that a beverage includes a particular amount of alcohol.One further communicates to the consumer that the alcohol in thebeverage will provide for less disagreeable physical effects than atypical beverage including the particular amount of alcohol. Thebeverage comprises water and at least 1.0 percent of a deuteratedalcohol according to Formula 1.

The consumer targeted by the method can be a person who wishes todecrease the deleterious side effects of a hangover; it can be a personhaving an enzyme abnormality related to the metabolism of ethanol; or itcan be a person who is concerned about a different aspect of analcohol-containing beverage. The compositions marketed according to thismethod include any composition encompassed by this document.

Experimental

The subject was a 52-year-old white Caucasian male, 154 kg, with noknown abnormalities of ethanol metabolism. Experiments were conductedafter an overnight fast. 1,1-Dideuterioethanol, 99 atom % D (CDNIsotopes; Quebec, Canada) (70 mL) was diluted to 500 mL with orangejuice, and the resulting beverage was consumed by the subject over thecourse of five minutes. The mouth and palate were rinsed with orangejuice, and data points were then obtained, in triplicate, every 10minutes with a commercial breath analyzer (AlcoHAWK™ Pro, Q3 InnovationsInc., Independence, Iowa, U.S.A.) The control experiment employed 175 mLof commercial vodka (80 proof; 40% ethanol) but was otherwise identical.

Measured blood levels as a function of time are presented in FIG. 1.Each data point in the FIGURE is the average of the three measurementstaken at each time point. The substantially equivalent areas under thecurves suggest that the analyzer is equally sensitive to ordinary anddeuterated ethanols.

The results from the control experiment are qualitatively similar tothose reported by previous workers (see, e.g., Milne et al., Am. J.Clin. Nutr., 1987, 46:688-693.) It is evident from FIG. 1, however, thatthe absorption of deuterated ethanol is substantially retarded, relativeto ethanol having a natural isotopic abundance, and that the rate ofclearance is reduced.

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise that as specifically described herein.

We claim:
 1. A method of making an alcoholic beverage, comprising thestep of adding to a beverage a deuterated alcohol having the formula

wherein each H may independently be hydrogen or deuterium; and, thebeverage is suitable for human consumption and, comprises: water andethanol, wherein at least 5 mole percent of the ethanol is the addeddeuterated alcohol.
 2. The method according to claim 1, wherein thedeuterated alcohol has the formula


3. The method according to claim 1, wherein the deuterated alcohol hasthe formula


4. The method according to claim 1, wherein the deuterated alcohol hasthe formula


5. The method according to claim 1, wherein the deuterated alcohol hasthe formula CD₃CD₂OH.
 6. The method of claim 1, wherein from 1 to 40% byweight of the beverage is ethanol.
 7. The method of claim 1, wherein atleast 15 mole percent of the ethanol is said deuterated alcohol.
 8. Themethod of claim 1, wherein at least 30 mole percent of the ethanol issaid deuterated alcohol.
 9. The method of claim 1, wherein at least 50mole percent of the ethanol is said deuterated alcohol.
 10. The methodof claim 1, wherein at least 75 mole percent of the ethanol is saiddeuterated alcohol.
 11. The method of claim 1, wherein at least 95 molepercent of the ethanol is said deuterated alcohol.
 12. The method ofclaim 1, wherein from 0.25 to 60% by weight of the beverage isdeuterated ethanol.
 13. The method of claim 1, wherein the beverage,further comprises: an additional component suitable for the alcoholicbeverage.
 14. The method of claim 1, wherein the beverage, furthercomprises: a sweetener that is suitable for the alcoholic beverage. 15.The method of claim 1, wherein the beverage, further comprises: anodorant that is suitable for the alcoholic beverage.
 16. The method ofclaim 1, wherein the beverage, further comprises: a flavorant that issuitable for the alcoholic beverage.
 17. The method of claim 1, whereinthe beverage, further comprises: a congener derived from a brewed orfermented composition that is suitable for the alcoholic beverage.